Genomic Based Drug Discovery
The Broad Institute assembled an Interdisciplinary Research Consortium with the goal of developing a new paradigm for drug discovery and development that begins and ends with patients. The Consortium drew from advances in human biology (especially genetics and physiology) and combined novel chemicals (small molecules) with innovative high-throughput screening methods that focused on how these molecules affect cells and organisms. These effects were either phenotypic (how the cells looked or behaved), or genetic (what genes the cells expressed). Additional methods were developed to help researchers identify the mechanism-of-action of these small molecules and to reveal potential toxicity issues early in the development cycle. These techniques were used to identify potential new therapeutics for cancer, psychiatric disease, and other complex medical conditions.
Consortium Director and Scientists
Scherer, Christina, 5UL1DE019585-04: GENOMICS BASED DRUG DISCOVERY
Golub, Todd, 1RL1CA133834-01: DISCOVERY PIPELINE
Schreiber, Stewart, 1RL1HG004671-01: TARGET ID
Scolnick, Edward, 1RL1GM084437-01: DRIVING MEDICAL PROJECTS
- Raj L, Ide T, Gurkar AU, Foley M, Shenone M, Li X, Tolliday NJ, Golub TR, Carr SA, Shamji AF, Stern AM, Mandinova A, Schreiber SL, and Lee SW. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 2011; 475(7355):231-4. PMID: 21753854.
- Fomina-Yadlin D, Kubicek S, Walpita D, Dančík V, Hecksher-Sørensen J, BittkerJA, Sharifnia T, Shamji A, Clemons PA, Wagner BK, and Schreiber SL. Small molecule inducers of insulin expression in pancreatic alpha cells. (2010) Proc. Natl. Acad. Sci. USA 107:15099-15104. PMID: 20696901.
- Comer E, Liu H, Joliton A, Clabaut A, Johnson C, Akella LB, and Marcaurelle LA. Organic Synthesis Toward Small-Molecule Probes and Drugs Special Feature: Fragment-based domain shuffling approach for the synthesis of pyranbased macrocycles. (2011) Proc. Natl. Acad. Sci. U S A. Mar 7 [Epub ahead of print]. PMID: 21383141.
- Pan JQ, Lewis MC, Ketterman JK, Clore EL, Riley M, Richards KR, Berry-Scott E, Liu X, Wagner FF, Holson EB, Neve RL, Biechele TL, Moon RT, Scolnick EM, Petryshen TL, and Haggarty SJ. AKT Kinase Activity Is Required for Lithium to Modulate Mood-Related Behaviors in Mice. Neuropsychopharmacology. (2011) Mar 9. [Epub ahead of print]. PMID:21389981
- Kuai, L, Ong, S.E., Madison, J.M., Wang, X, Duvall, J.R., Lewis, T.A., Luce,C.J., Conner, S.D., Pearlman, D.A., Wood, J.L., Schreiber, S.L., Carr, S.A., Scolnick, E.M. and Haggarty, S.J. (2011). Identification of AAK1 as an Inhibitor of Neuregulin-1/ErbB4-Dependent Neurotrophic Factor Signaling Using Integrative Chemical Genomics and Proteomics. (2011) Chemistry & Biology. (in press).